Medial prefrontal cortex (mPFC) dopamine (DA) modulates the motor-stimulant response to cocaine. The present study examined the specific mPFC DA receptor subtypes that mediate this behavioral response. Intra-mPFC injection of the DA D-2-Iike receptor agonist quinpirole blocked cocaine-induced motor activity, an effect that was prevented by coadministration of the D-2 receptor antagonist sulpiride. Intra-mPFC injection of the selective D-4 receptor agonist PD 168,077 or the selective D-3 receptor agonist SKF 81297 did not alter the motor-stimulant response to cocaine. Finally, it was found that an intermediate dose of quinpirole. which only attenuated cocaine-induced motor activity, was not altered by SKF 81297 coadministration. suggesting a lack of synergy between mPFC D-1 and D-2 receptors. These results suggest that D-2 receptor mechanisms in the mPFC are at least partly responsible for mediating the acute motor-stimulant effects of cocaine.